P957: CARFILZOMIB, LENALIDOMIDE, DEXAMETHASONE FOLLOWED BY A SECOND AUTO-HCT IS AN EFFECTIVE STRATEGY IN FIRST RELAPSE MULTIPLE MYELOMA: A STUDY OF THE CHRONIC MALIGNANCIES WORKING PARTY OF EBMT
Authors: R. Tilmont, I. Yakoub-Agha, D.-J. Eikema, N. Zinger, M. Haenel, N. Schaap, C. Herrera Arroyo, C. Schuermans, W. Bethge, M. Engelhardt, J. Kuball, M. Michieli, N. Schub, K. M. O. Wilson, J. H. Bourhis, M. V. Mateos, N. Robin, E. Jost, N. Kröger, J. M. Moraleda, S. Sica, P. J. Hayden, M. Beksac, S. Schönland, S. Manier
Journal: HemaSphere (2022)

Background: Multiple myeloma (MM) is an incurable hematologic malignancy despite recent therapeutic advances. In the context of lenalidomide-sensitive relapse, one of the preferred options from EHA/ESMO and IMWG recommendations is the combination of carfilzomib-lenalidomide-dexamethasone (KRd). This regimen has been approved based on the ASPIRE trial with a PFS of 26.3 months vs 17.6 months for Rd alone (HR = 0.69, p=0.0001). In younger patients, a second autologous hematopoietic cell transplantation (auto-HCT) remains an option in case of a prolonged remission after frontline auto-HCT. Only few data are available on the combination of KRd followed by a second auto-HCT in first relapse. Aims: Primary objective was to estimate progression-free survival (PFS) and overall survival (OS) in patients who received a second line of treatment with KRd followed by a second auto-HCT. Secondary objectives were to assess the response rates and identify statistically significant co-variables on PFS and OS in this population. Methods: This international retrospective study was performed in 22 centers affiliated to the European Society for Blood and Marrow Transplant Society (EBMT). Patients with MM were included if they received a second line of treatment with KRd induction followed by a second auto-HCT between January 2016 and December 2018. Results: A total of 51 patients were included, with a median age of 62 years (range 35 – 69). ISS at diagnosis was stage I for 18 patients (35.3%), stage II for 11 (21.6%),stage III for 14 (27.5%) and missing for 8 patients (15.7%). Twenty-seven patients (52.9%) were of standard cytogenetic risk and 11 patients (21.6%) of high cytogenetic risk according to IMWG criteria, data was missing for 13 patients (25.5%). The median time between the 1st to the 2nd transplant was 40.4 months (range 17.9–87.9). Regarding the number of cycles of KRd received in induction, 25 patients received 3 or 4 cycles (49.0%), 17 patients 5 or 6 cycles (33.3%) and 9 patients 7 to 12 cycles (17.7%). The conditioning chemotherapy was melphalan alone in 46 patients (90.2%), a combination of melphalan and another drug in 4 patients (7.8%) and cyclophosphamide alone in 1 patient (2.0%). The median follow-up was 36.7 months (range 5.3-58.0). The median PFS was 32.6 months (95%CI: 30–39.9) and the median OS was not reached, while 36- and 48-months OS rates were 87.5% (95%CI: 78.5–97.4) and 72.8% (95%CI: 57.0–92.8) respectively. In univariate analysis, 2 co-variates were found to be associated with a longer median PFS: an interval between the first and the 2nd auto-HCT of more than 4 years (mPFS of 36.1 vs. 30.6 months, p = 0.02) and the achievement of a very good partial response (VGPR) or better at the 2nd transplant (mPFS of 33.5 vs. 27.8 months, p = 0.01). These results were also observed in multivariate analysis, with HR of 0.41 (95%CI: 0.17-0.96, p = 0.04) and HR of 0.45 (95%CI: 0.21-0.98, p = 0.04), respectively. No statistical association was found between the duration of PFS and cytogenetic risk profile, with the limitation of a small number of patients with high-risk cytogenetics. Regarding OS, no significantly relevant co-variables were found in uni- or multivariate analysis. Image:Summary/Conclusion: A second auto-HCT after KRd induction is an effective treatment for patients with a first lenalidomide-sensitive relapse of MM. Our study suggests that patients with at least 4 years of remission after a frontline auto-HCT and who achieved at least a VGPR after KRd induction, benefit the most from this treatment strategy.